How Kaposi's sarcoma-associated herpesvirus stably transforms peripheral B cells towards Lymphomagenesis

Primary Effusion Lymphomas (PELs) are causally associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and 90% of PELs are co-infected with Epstein-Barr virus (EBV). Understanding how PELs develop has been impaired by the difficulty of infecting B cells with KSHV in vitro, and the inability of KSHV to transform them. We show that EBV supports an optimal co-infection of 2.5% of peripheral B cells by KSHV. We demonstrate for the first time that dually infected B cells are stably transformed in vitro and show that while both viruses can be maintained, different cells exhibit distinct, transformed properties. Transformed cells that grow to predominate in a culture express increased levels of most KSHV genes and differentially express a subset of cellular genes as do bona fide PEL cells.